Chemical proteomics unveils that seventy flavors pearl pill ameliorates ischemic stroke by regulating oxidative phosphorylation.

Ischemic stroke has high mortality and morbidity rates and is the second leading cause of death in the world, but there is no definitive medicine. Seventy Flavors Pearl Pill (SFPP) is a classic formula in Tibetan Medicine. Clinical practice has shown the attenuation effect of SFPP on blood pressure disorders, strokes and their sequelae and other neurological symptoms, but its mechanism remains to be elucidated. In this study, we established three animal models in vivo and three cell models to evaluate the anti-hypoxia, anti-ischemia, and reperfusion injury prevention effects of SFPP. Quantitative proteomics revealed that oxidative phosphorylation (OXPHOS) is essential for SFPP's efficacy. Then, cysteine-activity based protein profiling technology, which reflects redox stress at the proteome level, was employed to illustrate that SFPP brought functional differences of critical proteins in OXPHOS. In addition, quantitative metabolomics revealed that SFPP affects whole energy metabolism with OXPHOS as the core. Finally, we performed a compositional identification of SFPP to initially explore the components of potential interventions in OXPHOS. These results provide new perspectives and tools to explore the mechanism of herbal medicine. The study suggests that OXPHOS could be a potential target for further research and intervention of ischemic stroke treatment.

Proteomics and Metabolomics Unveil Codonopsis pilosula (Franch.) Nannf. Ameliorates Gastric Precancerous Lesions via Regulating Energy Metabolism.

Objective: This study aimed to systematically evaluate the efficacy of Codonopsis pilosula (Franch.) Nannf. (Codonopsis Radix, CR) and reveal the mechanism of its effects on suppressing Gastric Precancerous Lesions. Methods: First, we established the GPL rat model which was induced by N-methyl-N'-nitro-N-nitrosoguanidine, a disordered diet, and 40% ethanol. The CR's anti-Gastric Precancerous Lesions effect was comprehensively evaluated by body weight, pathological section, and serum biochemical indexes. Then, quantitative proteomics and metabolomics were conducted to unveil the disturbed protein-network and pharmacodynamic mechanism. Furthermore, serum pharmacology was employed to confirm that CR's anti-gastritis and anti-cancer phenotype in cell models. Results: In animal models, CR had been shown to control inflammation and ameliorate Gastric Precancerous Lesions. Considering the combination of proteomics and metabolomics, we found that CR could significantly reverse the biological pathways related to energy metabolism which were disturbed by the Gastric Precancerous Lesions model. Furthermore, the results of serum pharmacology indicated that the Codonopsis Radix containing serum could ameliorate gastritis injury and selectively inhibit the proliferation of gastric cancer cells rather than normal cells, which was closely related to ATP production in the above mentioned cells. Conclusion: In summary, CR exerted anti-Gastric Precancerous Lesions effects by ameliorating gastritis injury and selectively inhibiting the proliferation of gastric cancer cells rather than normal cells. Proteomics and metabolomics unveiled that its efficacy was closely related to its regulation of the energy-metabolism pathway. This research not only provided new ideas for exploring the mechanism of complex systems such as Chinese herbals but also benefited the treatment strategy of Gastric Precancerous Lesions via regulating energy metabolism.

A nano silicon adjuvant enhances inactivated transmissible gastroenteritis vaccine through activation the Toll-like receptors and promotes humoral and cellular immune responses.

Inactivated transmissible gastroenteritis virus (TGEV) vaccines are widely used in swine herds in China. These are limited, however, by the need to elicit both humoral and cellular immunity, as well as the efficiency of adjuvants. In this study, a 70-nm nano silicon particle was applied with inactivated TGEV vaccine in mice, and its immune-enhancing effects and mechanism of action investigated. We found that nano silicon applied with inactivated TGEV vaccine induced high antibody titers, increase IL-6, TNF-α and IFN-γ expression, and stimulate CD3+ T cell proliferation with a high CD4+/CD8+ T lymphocyte ratio. Nano silicon could quickly activate innate and adaptive immunity by stimulating Toll-like receptor signaling pathways, indicating that the nano silicon adjuvant enhanced long-term humoral and early cellular immune responses when combined with inactivated TGEV vaccine. Nano silicon could be considered for use as an antigen- carrier and adjuvant for veterinary vaccines.

Relationship between cystatin C and metabolic syndrome among Chinese premenopausal and postmenopausal women without recognized chronic kidney disease.

OBJECTIVE: Although studies have shown that elevated cystatin C (Cys-C) levels are associated with the risk of metabolic syndrome (MetS) in the general population, few studies have examined the relationship between serum Cys-C levels and MetS, stratified by menopause status, among women in China. Therefore, we conducted this study to assess the relationship between Cys-C levels and MetS in Chinese premenopausal and postmenopausal women. METHODS: We performed a cross-sectional analysis of the baseline data of 1,428 Chinese community-dwelling women who participated in the annual health checkup. MetS was defined by the updated National Cholesterol Education Program/Adult Treatment Panel III criteria. Binary logistic regression analysis was performed to estimate the association between Cys-C levels and MetS. One-way analysis of variance, followed by posttest for linear trends, was performed to evaluate the relationships between Cys-C levels and the number of MetS components. Ordinal regression analysis was used to determine whether menopause status and MetS components contribute to elevated levels of Cys-C. RESULTS: The mean level of Cys-C was significantly higher in women with MetS than in those without MetS among both premenopausal and postmenopausal women, showing a progressive increase (P for trend < 0.001) in parallel with the progressive increment in the number of MetS components in all women. Higher Cys-C levels were found to be associated with the presence of MetS after adjusting for age, body mass index, and estimated glomerular filtration rate in all women. The higher odds ratio changed little, even after further adjustment for serum blood nitrogen, total cholesterol, low-density lipoprotein cholesterol, drinking status, and smoking status. Elevated Cys-C level was significantly associated with postmenopause status (P = 0.007), increased waist circumference (P = 0.006), and elevated blood pressure (P = 0.025). CONCLUSIONS: Higher serum Cys-C levels are positively and independently associated with the presence of MetS in Chinese premenopausal and postmenopausal women. Elevated Cys-C levels are significantly associated with postmenopause status.

In vivo real-time freehand palpation imaging.

Previous experience with laboratory fixtures and off-line processing of elasticity data showed that problems occurring in data acquisition often resulted in poor elasticity image quality. A system for real-time estimation and display of tissue elastic properties using a clinical ultrasonic imaging system has been developed. A brief description of that system and the initial clinical tests of that system are reported. Experience with real-time freehand elasticity imaging shows that images with high contrast-to-noise ratios are consistently obtained. Images of breast lesions were acquired with freehand palpation using standard linear-array ultrasound (US) transducers. Results in volunteer patients show that high-quality elasticity images are easily obtained from in vivo breast studies. The key element to successful scanning is real-time visual feedback of B-mode and strain images that guide the patient positioning and compression direction. Results show that individual images of axial strain in tissues can be quite misleading, and that a "movie loop" of side-by-side B-mode and strain images provides significantly more information. Our preliminary data suggest that the strain image sequences for various breast pathologies are unique. For example, strain images of fibroadenomas lose contrast with increasing precompression, but those of invasive ductal carcinoma have high negative contrast (dark relative to "normal" tissue) for a wide range of precompression. In addition, a comparison of the lesion area measured in B-mode vs. strain images, for a representative image from the sequence, appears to be a sensitive criterion for separating invasive ductal carcinoma from cyst and fibroadenoma.

A modified block matching method for real-time freehand strain imaging.

This manuscript reports a technical innovation that has been developed for real-time, freehand strain imaging. This work is based on a well-known block-matching algorithm with two significant modifications. First, since displacements are estimated row-by-row, displacement estimates from the previous row are used to predict the displacement estimates in the current row, thereby drastically reducing the search-region size and increasing computational efficiency. Second, a displacement error detection and correction method is developed to overcome the local tracking errors that may be more severe with freehand scanning and thereby improve the robustness of the algorithm. This algorithm has been implemented on a clinical ultrasound imaging system, and with real-time imaging feedback, long sequences of high quality strain images are observed using freehand compression. Displacement estimation errors with this method are experimentally measured and compared with results from simulation. We report only a specific implementation, with no comparison to other displacement estimators in the literature and no optimization of this specific technique. Images of tissue-mimicking phantoms with small spherical targets are used to test the ability to detect small lesions using the strain imaging technique. In vivo strain images of breast and thyroid are also shown.